The mechanism mediating reticuloendothelial system (R.E.S.) depression following surgery and whole body trauma was studied in animals and humans. Phagocytic activity was evaluated by the clearance of a test colloid and plasma opsonic activity was determined by bioassay. In rats, R.E.S. failure was apparent within 30-60 minutes following whole body trauma (Noble-Collip) and the degree of R.E. depression was closely correlated with the extent of trauma. Following sublethal shock, recovery of the R.E.S. was complete by 24 hours and associated with host survival. In contrast, progressive deterioration of the R.E.S. was observed following lethal trauma. Systemic hypo-opsonemia was related to R.E. depression while recovery of plasma opsonin was associated with R.E. recovery. Opsonic depletion appeared to be a function of the degree of trauma and the overall R.E.S. clearance depression was primarily due to hepatic phagocytic failure. Regional blood flow alterations were observed following trauma, especially a decrease in splanchnic blood flow, but R.E. depression still existed in the presence of flow recovery. However, a close correlation existed between the elevation of plasma lysosomal enzymes and the extent of R.E. failure. In addition, animals manifested decreased bacterial clearance when challenged during a period of post-injury R.E. depression. In 16 patients studied, it was observed that patients which recovered rapidly following trauma, also demonstrated a progressive recovery of the plasma opsonin level. In contrast, patients which did not recover, manifested prolonged hypo-opsonemia and sepsis. Opsonic protein is a thermolabile, heparin dependent alpha-2-glycoprotein of large molecular weight. Thus, R.E. depression exists following trauma and opsonic protein administration may provide a selective method to circumvent such R.E. failure. BIBLIOGRAPHIC REFERENCES: Saba, T.M. and Scovill, W.A. Effect of surgical trauma on host defense. Surgery Annual (ed) L. Nyhus, Appleton Century-Crofts, Vol. 7, pp. 71-102, 1975; Cornell, R.P. and Saba, T.M. Degradation of particulate lipid by large granule fraction in liver. Proc. Soc. Exp. Biol. Med. 148: 430-434, 1975.